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Hepatitis C virus RNA functionally sequesters miR-122.
Luna, Joseph M; Scheel, Troels K H; Danino, Tal; Shaw, Katharina S; Mele, Aldo; Fak, John J; Nishiuchi, Eiko; Takacs, Constantin N; Catanese, Maria Teresa; de Jong, Ype P; Jacobson, Ira M; Rice, Charles M; Darnell, Robert B.
Afiliação
  • Luna JM; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
  • Scheel TK; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Disease and Clinical Research Centre, Copenhagen University Hospital, Hvidovre, and Department of
  • Danino T; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Shaw KS; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
  • Mele A; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
  • Fak JJ; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
  • Nishiuchi E; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
  • Takacs CN; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY 10065, USA.
  • Catanese MT; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
  • de Jong YP; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Center for the Study of Hepatitis C, Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10065, USA.
  • Jacobson IM; Center for the Study of Hepatitis C, Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10065, USA.
  • Rice CM; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA. Electronic address: ricec@rockefeller.edu.
  • Darnell RB; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA; New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA. Electronic address: darnelr@rockefeller.edu.
Cell ; 160(6): 1099-110, 2015 Mar 12.
Article em En | MEDLINE | ID: mdl-25768906
ABSTRACT
Hepatitis C virus (HCV) uniquely requires the liver-specific microRNA-122 for replication, yet global effects on endogenous miRNA targets during infection are unexplored. Here, high-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) experiments of human Argonaute (AGO) during HCV infection showed robust AGO binding on the HCV 5'UTR at known and predicted miR-122 sites. On the human transcriptome, we observed reduced AGO binding and functional mRNA de-repression of miR-122 targets during virus infection. This miR-122 "sponge" effect was relieved and redirected to miR-15 targets by swapping the miRNA tropism of the virus. Single-cell expression data from reporters containing miR-122 sites showed significant de-repression during HCV infection depending on expression level and site number. We describe a quantitative mathematical model of HCV-induced miR-122 sequestration and propose that such miR-122 inhibition by HCV RNA may result in global de-repression of host miR-122 targets, providing an environment fertile for the long-term oncogenic potential of HCV.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Viral / Hepatite C / Hepacivirus / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Viral / Hepatite C / Hepacivirus / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article